UTILITY OF URINARY BIOMARKERS IN THE DIAGNOSIS AND PROGNOSIS OF CHILDREN WITH HYDRONEPHROSIS

Introduction:

Hydronephrosis refers to the dilation of the renal pelvis with or without calyceal dilation. In various studies, the overall prevalence of antenatally detected hydronephrosis ranges from 0.6-5.4%. Non-obstructive dilatation (NOD) due to transient hydronephrosis is the most common cause of urinary tract dilatation in children, followed by ureteropelvic junction obstruction (UPJO). Differentiating children with self-resolving physiological dilatation and those with pathological obstruction heralding significant renal impairment still remains a topic of extensive debate. Metabolomics is an evolving field, which has been recently applied in the diagnosis of UPJO. This has the potential to distinguish patients with UPJO requiring surgery from those with non-obstructive transient dilatation and healthy controls.

Methods:

It was a prospective case-control study performed at tertiary-care hospital in South India. The aim of the study was to compare the utility of urinary biomarkers: carbohydrate antigen (CA 19-9), neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule (KIM) in diagnosing UPJO. The objectives was to determine the utility of urinary biomarkers in NOD from UPJO and to determine the role of urinary biomarkers in the prognosis of children with UPJO post-pyeloplasty.

The sample size was calculated based on the previous studies predicting the need for pyeloplasty using the sensitivity and specificity of biomarkers CA 19-9, NGAL and KIM. With 15% relative precision and 95% confidence interval, the minimal sample size required was 32 in the UPJO group, 38 for the NOD and healthy control group each.

Descriptive statistics like median and standard error mean were calculated. The Kruskal-Wallis test was used to identify significant differences in the study group and control; and preoperative and postoperative values of each marker. Scatter-plots were generated, and correlation coefficients were calculated to investigate mutual relationship between biomarker and USG APD.

Results:

Urinary CA 19-9, NGAL and KIM-1 levels were higher in UPJO group compared to NOD and controls (p<0.05). Scatter-plots revealed positive correlation between biomarker levels and USG APD, both pre-operatively and post-operatively. Urine CA 19-9 cut-off of 90.67 U/mL showed the sensitivity and specificity of 95% and 96% with AUC of 0.988 for diagnosing UPJO. Urinary NGAL cut off of 19.78 pg/mL had the sensitivity, specificity and area under the curve as 88%, 68% and 0.901 respectively. Urinary KIM 1 of 489.71 pg/mL cut-off gave the sensitivity of 76% and specificity of 45% with AUC of 0.640 (Fig.1). Post-operative biomarker levels showed statistically significant drop (p <0.05) compared to pre-operative values (Fig.2). Combining all three biomarkers, improved the diagnostic ability of the biomarker panel with a specificity of 99.29%. These combinations did not show much improvement in the sensitivity of the biomarkers.

Conclusions:

Urinary CA 19-9 is superior to NGAL and KIM in identifying children with UPJO. Combining all three biomarkers/ USG APD with individual biomarkers showed an increase in the diagnostic ability of the biomarker panel. These biomarkers may emerge as a non-invasive and safe method for postoperative follow-up of these children.

I have potential conflict of interest to disclose.
This study was supported by Indian Council of Medical Research, Grant in AID project

I did not use generative AI and AI-assisted technologies in the writing process.